Extracellular cleavage of cadherin-11 by ADAM metalloproteases is essential for Xenopus cranial neural crest cell migration.
Cell adhesion molecules such as cadherins alternate their expression throughout cranial neural crest (CNC) development, yet our understanding of the role of these molecules during CNC migration remains incomplete. The "mesenchymal" cadherin-11 is expressed in the CNC during migration yet prevents migration when overexpressed in the embryo, suggesting that a defined level of cadherin-11-mediated cell adhesion is required for migration. Here we show that members of the meltrin subfamily of ADAM metalloproteases cleave the extracellular domain of cadherin-11 during CNC migration. We show that a fragment corresponding to the putative shed form of cadherin-11 retains biological activity by promoting CNC migration in vivo, in a non-cell-autonomous manner. Additionally, cleavage of cadherin-11 does not affect binding to beta-catenin and downstream signaling events. We propose that ADAM cleavage of cadherin-11 promotes migration by modifying its ability to support cell-cell adhesion while maintaining the membrane-bound pool of beta-catenin associated with the cadherin-11 cytoplasmic domain.
McCusker
Catherine
C
Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003, USA.
Cousin
Hélène
H
Neuner
Russell
R
Alfandari
Dominique
D
D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D017403:In Situ Hybridization; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D009024:Morphogenesis / Q000502:physiology; D009432:Neural Crest / Q000166:cytology / Q000502:physiology; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D014982:Xenopus laevis / Q000033:anatomy & histology / Q000196:embryology
D015820:Cadherins; D007527:Isoenzymes; D008164:Luminescent Proteins; D016376:Oligonucleotides, Antisense; D051153:Wnt Proteins; C086960:osteoblast cadherin; D051722:ADAM Proteins